Despite extensive research efforts, the development of an effective treatment drug for cocaine addiction continues to be a difficult task. Based on the dopamine transporter (DAT) theory of cocaine addiction, several dopaminergic drugs have been tested in the past with no apparent success. Recent experimental evidence suggests that besides dopamine, serotonin also may play some role in cocaine's pharmacological effects. Thus, one approach would be to develop molecules that simultaneously inhibit both DAT and 5-HTT with a wide range of selectivities and to investigate their potential as possible treatment drugs for cocaine addiction. Towards this goal, several new cocaine analogs that inhibit both DAT and 5-HTT with a range of selectivity ratios have been synthesized using a lead compound namely, Trans (+) 4-chlorophenyl piperidine 3-carboxilic acid, [(+)- CPCA], a piperidine-based cocaine analog. The (+)-CPCA was used as a parent compound because of its desirable pharmacological profile. The specific aim of the present proposal is to evaluate the behavioral pharmacology of these novel monoamine uptake inhibitors using locomotor activity, drug discrimination and intravenous drug self- administration tests. The long-term objective of the present proposal is to develop an effective treatment drug for cocaine addiction. Compounds with potential for the treatment of cocaine addiction are likely to result from this work. PROPOSED COMMERCIAL APPLICATION: Develop an effective treatment drug for cocaine addiction